SUMMARY of PRODUCT CHARACTERISTICS for Lovastatin

Total Page:16

File Type:pdf, Size:1020Kb

SUMMARY of PRODUCT CHARACTERISTICS for Lovastatin SUMMARY OF PRODUCT CHARACTERISTICS for Lovastatin Mylan tablets 1 NAME OF THE MEDICINAL PRODUCT Lovastatin Mylan 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Lovastatin 20 mg and 40 mg For a full list of excipients see section 6.1. 3 PHARMACEUTICAL FORM Tablets 20 mg: Pale blue, octagonal tablets marked “LV/20” on one side and “G” on the other, with score-line on one side. 40 mg: Green, octagonal tablets marked “LV/40” on one side and “G” on the other, with score-line on one side. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Severe cases of hypercholesterolaemia when dietary treatment does not have an adequate effect. 4.2 Posology and method of administration The patient should be placed on a standard cholesterol-lowering diet before being given lovastatin. This diet should be continued during treatment with lovastatin. Any cause for secondary hypercholesterolemia should be excluded before initiation of treatment. HYPERCHOLESTEROLEMIA: The initial dose is generally 20 mg per day, given as a single dose with the evening meal. It has been shown that single daily doses given with the evening meal are more effective than the same dose given with breakfast, possibly because cholesterol synthesis takes place mainly at night. Patients with mild to moderate hypercholesterolemia may be treated with an initial dose of 10 mg lovastatin. Any dosage adjustments should be made at intervals of at least 4 weeks. A maximum of 80 mg should be given daily in a single dose or divided into 2 doses taken with breakfast and the evening meal. Two daily doses would appear to be more effective than one daily dose. The dosage of lovastatin should be reduced if LDL-cholesterol levels drop below 75 mg/dL (1.94 mmol/L), or if total serum cholesterol concentrations fall below 140 mg/dL (3.6 mmol/L). CONCOMITANT TREATMENT Lovastatin is effective alone or in combination with bile-acid sequestrants. Page 1 of 11 In patients being given cyclosporine, danazol, gemfibrozil, other fibrates or lipid-lowering doses (≥ 1 g/day) of niacin at the same time as lovastatin, the maximum recommended dose is 20 mg/day. In patients taking amiodarone or verapamil concomitantly with lovastatin, the dose of lovastatin should not exceed 40 mg/day (see section 4.4. Special warnings and precautions for use Myopathy/Rhabdomyolysis and 4.5. Interactions with other medicinal products and other forms of interaction) DOSAGE IN RENAL INSUFFICIENCY Since lovastatin does not undergo significant renal excretion, moderate renal insufficiency does not necessitate any dosage reduction. In patients with severe renal failure (creatinine clearance <30 ml/min) dosages over 20 mg/day should be carefully considered, and, if necessary, should be commenced with caution (see section 4.4. Special warnings and precautions for use Myopathy/Rhabdomyolysis and 5.0 Pharmacological properties). USE IN CHILDREN AND ADOLESCENTS (< 18 YEARS): The use of lovastatin in children is not recommended, as safety and efficacy studies have not been established. USE IN THE ELDERLY In a controlled trial of the treatment of patients in the over-sixty age group, the effects appeared to be identical to those in the remainder of the population and there was no marked increase in frequency of clinical or laboratory adverse findings. 4.3 Contraindications Hypersensitivity to lovastatin or to any of the excipients of the medicinal product. Active liver disease or unexplained persistently elevated serum transaminase levels. Cholestasis Myopathy Concomitant administration of potent CYP3A4 inhibitors (itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone). Concomitant treatment with delavirdine, verapamil and amiodarone. Pregnancy and lactation (see section 4.6). Alcoholism 4.4 Special warnings and precautions for use Myopathy/Rhabdomyolysis: Lovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above 10X the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. - The risk of myopathy/rhabdomyolysis is increased by concomitant use of lovastatin with the following: Potent inhibitors of CYP3A4, e.g., mibefradil (a calcium antagonist of the tetralol type), itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, or nefazodone, particularly with higher doses of lovastatin (see Page 2 of 11 section 4.5. Interaction with other medicinal products and other forms of interaction, CYP3A4 Interactions and 5.2. Pharmacokinetic properties). Lipid-lowering drugs that can cause myopathy when given alone: Gemfibrozil, other fibrates, or lipid-lowering doses (_1 g/day) of niacin, particularly with higher doses of lovastatin (see section 4.5. Interaction with other medicinal products and other forms of interaction, Interactions with lipid-lowering drugs that can cause myopathy when given alone and 5.2. Pharmacokinetic properties). Cyclosporine or danazol particularly with higher doses of lovastatin. (see section 4.5. Interaction with other medicinal products and other forms of interaction, Other drug interactions and 5.2. Pharmacokinetic properties). Other drugs: Amiodarone or Verapamil: The risk of myopathy/rhabdomyolysis is increased when either amiodarone or verapamil is used concomitantly with higher doses of a closely related member of the HMG-CoA reductase inhibitor class (see section 4.5. Interaction with other medicinal products and other forms of interaction, Other drug interactions). Fusidic Acid: The risk of myopathy may be increased when fusidic acid is used concomitantly with a closely related member of the HMG-CoA reductase inhibitor class (see section 4.4. Special warnings and special precautions for use, Myopathy/Rhabdomyolysis and 5.2. “Pharmacokinetic properties”). HMG-CoA inhibitors and antifungal medicinal products, which are azole derivatives, inhibit cholesterol synthesis at different points in the synthesis chain. Patients who are receiving cyclosporin treatment should have lovastatin therapy withdrawn if systemic fungicide treatment with an azole derivative is necessary. Patients who are not receiving cyclosporin treatment should be carefully monitored if systemic fungicide treatment with an azole derivative is necessary. Lovastatin treatment must be temporarily interrupted or withdrawn in patients who have a condition which predisposes them to the development of renal failure, such as a serious acute infection, hypotension, major surgery, trauma, a severe metabolic, endocrine or electrolyte balance disorder or uncontrolled epilepsy. - As with other HMG-CoA reductase inhibitors, the risk of myopathy/rhabdomyolysis is dose related. In a clinical study (EXCEL) in which patients were carefully monitored and some interacting drugs were excluded, there was one case of myopathy among 4933 patients randomized to lovastatin 20-40 mg daily for 48 weeks, and 4 among 1649 patients randomized to 80 mg daily. Creatine Kinase measurement: Creatine Kinase (CK) should not be measured following strenuous exercise or in the presence of any plausible alternative cause of CK increase as this makes value interpretation difficult. If CK levels are significantly elevated at baseline (> 5xULN), levels should be re-measured within 5 to 7 days later to confirm the results. Before the treatment: All patients starting therapy with lovastatin, or whose dose of lovastatin is being increased, should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. Clinicians should prescribe statins with caution in patients with pre-disposing factors for rhabdomyolysis. In order to establish a reference baseline value, a creatine kinase (CK) level should be measured before starting statin treatment in the following situations: - Elderly (age >70 years) Page 3 of 11 - Renal impairment - Uncontrolled hypothyroidism - Personal or familial history of hereditary muscular disorders - Previous history of muscular toxicity with a statin or fibrate - Alcohol abuse In such situations the risk of treatment should be considered in relation to possible benefit and clinical monitoring is recommended. If a patient has previously experiences a muscle disorder on a fibrate or a statin, treatment with a different member of the class should only be initiated with caution. If CK levels are significantly elevated (> 5xULN) at baseline, treatment should not be started. Whilst on treatment: If muscular pain, weakness or cramps occur whilst a patient is receiving treatment with a statin, their CK levels should be measured. If these levels are found, in the absence of strenuous exercise, to be significantly elevated (>5xULN), treatment should be stopped. If muscular symptoms are severe and cause daily discomfort, even if CK levels are elevated to ≤ 5xULN, treatment discontinuation should be considered. If myopathy is suspected for any other reason, treatment should be discontinued. If symptoms resolve and CK levels return to normal, then re-introduction of the statin or introduction of an alternative statin may be considered at the lowest dose and with close monitoring. Therapy with lovastatin should be temporarily stopped a few days prior to elective major surgery and when any major medical
Recommended publications
  • Long-Term Statin Use and Risk of Ductal and Lobular Breast Cancer Among Women 55 to 74 Years of Age
    Published OnlineFirst July 5, 2013; DOI: 10.1158/1055-9965.EPI-13-0414 Cancer Epidemiology, Research Article Biomarkers & Prevention Long-Term Statin Use and Risk of Ductal and Lobular Breast Cancer among Women 55 to 74 Years of Age Jean A. McDougall1, Kathleen E. Malone1, Janet R. Daling1, Kara L. Cushing-Haugen1, Peggy L. Porter1,2, and Christopher I. Li1 Abstract Background: Mechanistic studies largely support the chemopreventive potential of statins. However, results of epidemiologic studies investigating statin use and breast cancer risk have been inconsistent and lacked the ability to evaluate long-term statin use. Methods: We used data from a population-based case–control study of breast cancer conducted in the Seattle–Puget Sound region to investigate the relationship between long-term statin use and breast cancer risk. Nine hundred sixteen invasive ductal carcinoma (IDC) and 1,068 invasive lobular carcinoma (ILC) cases in patients 55 to 74 years of age diagnosed between 2000 and 2008 were compared with 902 control women. All participants were interviewed in-person and data on hypercholesterolemia and all episodes of lipid-lowering medication use were collected through a structured questionnaire. We assessed the relationship between statin use and IDC and ILC risk using polytomous logistic regression. Results: Current users of statins for 10 years or longer had a 1.83-fold increased risk of IDC [95% confidence interval (CI): 1.14–2.93] and a 1.97-fold increased risk of ILC (95% CI: 1.25–3.12) compared with never users of statins. Among women diagnosed with hypercholesterolemia, current users of statins for 10 years or longer had more than double the risk of both IDC (OR: 2.04, 95% CI: 1.17–3.57) and ILC (OR: 2.43, 95% CI: 1.40–4.21) compared with never users.
    [Show full text]
  • What Precautions Should We Use with Statins for Women of Childbearing
    CLINICAL INQUIRIES What precautions should we use with statins for women of childbearing age? Chaitany Patel, MD, Lisa Edgerton, PharmD New Hanover Regional Medical Center, Wilmington, North Carolina Donna Flake, MSLS, MSAS Coastal Area Health Education Center, Wilmington, NC EVIDENCE- BASED ANSWER Statins are contraindicated for women who are on its low tissue-penetration properties. pregnant or breastfeeding. Data evaluating statin Cholesterol-lowering with simvastatin 40 mg/d did use for women of childbearing age is limited; how- not disrupt menstrual cycles or effect luteal phase ever, they may be used cautiously with adequate duration (strength of recommendation: C). contraception. Pravastatin may be preferred based CLINICAL COMMENTARY Use statins only as a last resort Before reading this review, I had not been for women of childbearing age ® Dowdenaware Health of the serious Media effects of statin medications I try to follow the USPSTF recommendations and on the developing fetus. In conversations with not screen women aged <45 years without coro- my colleagues, I found that the adverse effects nary artery disease riskCopyright factors for Fhyperlipidemia.or personalof usestatins onlyduring pregnancy are not readily When a woman of any age needs treatment, my known. Such information needs to be more first-line therapy is lifestyle modification. Given the widely disseminated. risks of statin drugs to the developing fetus, Ariel Smits, MD women with childbearing potential should give Department of Family Medicine, Oregon Health & Science fully informed consent and be offered reliable University, Portland contraception before stating statin therapy. I Evidence summary anal, cardiac, tracheal, esophageal, renal, Hydroxymethyl glutaryl coenzyme A and limb deficiency (VACTERL associa- (HMG CoA) reductase inhibitors, com- tion), intrauterine growth retardation monly called statins, have been on the (IUGR), and demise in fetuses exposed market since the late 1980s.
    [Show full text]
  • Dyslipidemia in Newfoundland: Findings from Canadian Primary Care Sentinel Surveillance Network in Newfoundland and Labrador
    Dyslipidemia in Newfoundland: Findings from Canadian Primary Care Sentinel Surveillance Network in Newfoundland and Labrador By Justin D. Oake A thesis submitted to the School of Graduate Studies in partial fulfillment of the requirements for the degree of Master of Science in Medicine Clinical Epidemiology Program, Faculty of Medicine, Memorial University of Newfoundland St. John’s, NL May 2019 Abstract Newfoundland and Labrador (NL) has a higher level of cardiovascular disease (CVD) mortality than any other Canadian province. One factor which may explain this trend is the lipid profile pattern in this province. Given the limited lipid profile data which has been reported from NL, we organized three studies in this thesis to describe the lipid profile of Newfoundlanders. The first study was a secondary analysis of Canadian Primary Care Sentinel Surveillance Network (CPCSSN) data to document single and mixed dyslipidemia in NL. The second study compared lipid profiles and the prevalence of dyslipidemia between NL CPCSSN data and the Canadian Health Measures Survey (CHMS). The third study used electronic medical record (EMR) data in assessing the validity of ICD codes for identifying patients with dyslipidemia. This was a secondary analysis of EMR data in NL. Most recent lipid profile scores, co-morbidities, and demographic information were extracted from the CPCSSN database. We demonstrated that single and mixed dyslipidemia are quite prevalent in the NL population. Unhealthy levels of HDL were also more prevalent in NL men, compared to the Canadian sample. Of importance, the use of the ICD coding, either alone or in combination with laboratory data or lipid-lowering medication records, was an inaccurate indicator in identifying dyslipidemia.
    [Show full text]
  • Effects of Generic Substitution on Refill Adherence to Statin Therapy: a Nationwide Population-Based Study Henrik Trusell1 and Karolina Andersson Sundell1,2*
    Trusell and Andersson Sundell BMC Health Services Research 2014, 14:626 http://www.biomedcentral.com/1472-6963/14/626 RESEARCH ARTICLE Open Access Effects of generic substitution on refill adherence to statin therapy: a nationwide population-based study Henrik Trusell1 and Karolina Andersson Sundell1,2* Abstract Background: Several countries have introduced generic substitution, but few studies have assessed its effect on refill adherence. This study aimed to analyse whether generic substitution influences refill adherence to statin treatment. Methods: Between 1 July 2006 and 30 June 2007, new users of simvastatin (n = 108,806) and atorvastatin (n = 7,464) were identified in the Swedish Prescribed Drug Register . The present study included atorvastatin users as an unexposed control group because atorvastatin was patent-protected and thus not substitutable. We assessed refill adherence using continuous measure of medication acquisition (CMA). To control for potential confounders, we used analysis of covariance (ANCOVA). Differences in CMA associated with generic substitution and generic substitution at first-time statin purchase were analysed. Results: Nine of ten simvastatin users were exposed to generic substitution during the study period, and their adherence rate was higher than that of patients without substitution [84.6% (95% CI 83.5-85.6) versus 59.9% (95% CI 58.4-61.4), p < 0.001]. CMA was higher with increasing age (60–69 years 16.7%, p < 0.0001 and 70–79 years 17.8%, p < 0.0001, compared to 18–39 years) and secondary prevention (12.8%, p < 0.0001). CMA was lower among patients who were exposed to generic substitution upon initial purchase, compared to those who were exposed to a generic substitution subsequently [80.4% (95% CI 79.4-90.9) versus 89.8% (88.7-90.9), p < 0.001].
    [Show full text]
  • Regulation of Pharmaceutical Prices: Evidence from a Reference Price Reform in Denmark
    A Service of Leibniz-Informationszentrum econstor Wirtschaft Leibniz Information Centre Make Your Publications Visible. zbw for Economics Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas Working Paper Regulation of pharmaceutical prices: Evidence from a reference price reform in Denmark ZEW Discussion Papers, No. 10-062 Provided in Cooperation with: ZEW - Leibniz Centre for European Economic Research Suggested Citation: Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas (2010) : Regulation of pharmaceutical prices: Evidence from a reference price reform in Denmark, ZEW Discussion Papers, No. 10-062, Zentrum für Europäische Wirtschaftsforschung (ZEW), Mannheim This Version is available at: http://hdl.handle.net/10419/41440 Standard-Nutzungsbedingungen: Terms of use: Die Dokumente auf EconStor dürfen zu eigenen wissenschaftlichen Documents in EconStor may be saved and copied for your Zwecken und zum Privatgebrauch gespeichert und kopiert werden. personal and scholarly purposes. Sie dürfen die Dokumente nicht für öffentliche oder kommerzielle You are not to copy documents for public or commercial Zwecke vervielfältigen, öffentlich ausstellen, öffentlich zugänglich purposes, to exhibit the documents publicly, to make them machen, vertreiben oder anderweitig nutzen. publicly available on the internet, or to distribute or otherwise use the documents in public. Sofern die Verfasser die Dokumente unter Open-Content-Lizenzen (insbesondere CC-Lizenzen) zur Verfügung gestellt haben sollten, If the documents have been made available under an Open gelten abweichend von diesen Nutzungsbedingungen die in der dort Content Licence (especially Creative Commons Licences), you genannten Lizenz gewährten Nutzungsrechte. may exercise further usage rights as specified in the indicated licence. www.econstor.eu Dis cus si on Paper No. 10-062 Regulation of Pharmaceutical Prices: Evidence from a Reference Price Reform in Denmark Ulrich Kaiser, Susan J.
    [Show full text]
  • Bempedoic Acid and Inclisiran for Patients with Heterozygous Familial Hypercholesterolemia and for Secondary Prevention of ASCVD: Effectiveness and Value
    Bempedoic Acid and Inclisiran for Patients with Heterozygous Familial Hypercholesterolemia and for Secondary Prevention of ASCVD: Effectiveness and Value Draft Evidence Report November 12, 2020 Prepared for ©Institute for Clinical and Economic Review, 2020 ICER Staff and Consultants Modeling Team Grace A. Lin, MD, MAS Dhruv S. Kazi, MD, MSc, MS Associate Professor of Medicine and Health Policy Associate Director, Smith Center for Outcomes University of California, San Francisco Research in Cardiology Director, Cardiac Critical Care Unit Jane Jih, MD, MPH Beth Israel Deaconess Medical Center Assistant Professor, Division of General Internal Associate Professor, Harvard Medical School Medicine University of California, San Francisco Foluso Agboola, MBBS, MPH Director, Evidence Synthesis Dr. Kazi was responsible for the development of the ICER cost-effectiveness model, interpretation of results, and drafting of the economic sections of this report; the Rick Chapman, PhD, MS resulting ICER reports do not necessarily represent the Director of Health Economics views of Beth Israel Deaconess Medical Center or ICER Harvard Medical School. Steven D. Pearson, MD, MSc President ICER DATE OF PUBLICATION: November 12, 2020 How to cite this document: Lin GA, Kazi DS, Jih J, Agboola F, Chapman R, Pearson SD. Inclisiran and Bempedoic Acid for Patients with Heterozygous Familial Hypercholesterolemia and for Secondary Prevention of ASCVD: Effectiveness and Value; Draft Evidence Report. Institute for Clinical and Economic Review, November 12, 2020. https://icer-review.org/material/high-cholesterol-update- draft-evidence-report/ Grace Lin served as the lead author for the report and wrote the background, other benefits, and contextual considerations sections of the report, with Jane Jih serving as a co-author.
    [Show full text]
  • Protective Lipid-Lowering Genetic Variants in Healthy Older Individuals Without Coronary
    medRxiv preprint doi: https://doi.org/10.1101/2021.02.16.21251811; this version posted February 19, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . TITLE PAGE Title: Protective lipid-lowering genetic variants in healthy older individuals without coronary heart disease Running title: Lacaze - Protective lipid-lowering variants Authors: Paul Lacaze, PhD1*, Moeen Riaz, PhD1, Robert Sebra, PhD2, Amanda J Hooper, PhD3,4, Jing Pang, PhD3, Jane Tiller, LLB, MSc GenCoun1, Galina Polekhina, PhD1, Andrew M Tonkin, PhD1, Christopher M Reid, PhD1,5, Sophia Zoungas, MD, PhD1, Anne M Murray, MD, MSc6, Stephen J Nicholls MD, PhD7, Gerald F Watts, MD, PhD4,8, Eric Schadt, PhD2 & John J McNeil, MD, PhD1 Departments and institutions: 1 Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. 2 Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, USA. 3 School of Medicine, Faculty of Medicine and Health Sciences, The University of Western Australia, Perth, Australia 4 Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Western Australia, Australia. 5 School of Public Health, Curtin University, Perth, WA, Australia 6 Berman Center for Outcomes and Clinical Research, Hennepin Healthcare Research Institute, Hennepin Healthcare, Minneapolis, MN, USA 7 Monash Cardiovascular Research Centre, Monash University and MonashHeart, Monash Health, Clayton, Victoria, Australia; 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
    [Show full text]
  • 2021 Formulary List of Covered Prescription Drugs
    2021 Formulary List of covered prescription drugs This drug list applies to all Individual HMO products and the following Small Group HMO products: Sharp Platinum 90 Performance HMO, Sharp Platinum 90 Performance HMO AI-AN, Sharp Platinum 90 Premier HMO, Sharp Platinum 90 Premier HMO AI-AN, Sharp Gold 80 Performance HMO, Sharp Gold 80 Performance HMO AI-AN, Sharp Gold 80 Premier HMO, Sharp Gold 80 Premier HMO AI-AN, Sharp Silver 70 Performance HMO, Sharp Silver 70 Performance HMO AI-AN, Sharp Silver 70 Premier HMO, Sharp Silver 70 Premier HMO AI-AN, Sharp Silver 73 Performance HMO, Sharp Silver 73 Premier HMO, Sharp Silver 87 Performance HMO, Sharp Silver 87 Premier HMO, Sharp Silver 94 Performance HMO, Sharp Silver 94 Premier HMO, Sharp Bronze 60 Performance HMO, Sharp Bronze 60 Performance HMO AI-AN, Sharp Bronze 60 Premier HDHP HMO, Sharp Bronze 60 Premier HDHP HMO AI-AN, Sharp Minimum Coverage Performance HMO, Sharp $0 Cost Share Performance HMO AI-AN, Sharp $0 Cost Share Premier HMO AI-AN, Sharp Silver 70 Off Exchange Performance HMO, Sharp Silver 70 Off Exchange Premier HMO, Sharp Performance Platinum 90 HMO 0/15 + Child Dental, Sharp Premier Platinum 90 HMO 0/20 + Child Dental, Sharp Performance Gold 80 HMO 350 /25 + Child Dental, Sharp Premier Gold 80 HMO 250/35 + Child Dental, Sharp Performance Silver 70 HMO 2250/50 + Child Dental, Sharp Premier Silver 70 HMO 2250/55 + Child Dental, Sharp Premier Silver 70 HDHP HMO 2500/20% + Child Dental, Sharp Performance Bronze 60 HMO 6300/65 + Child Dental, Sharp Premier Bronze 60 HDHP HMO
    [Show full text]
  • Exploitation of Aspergillus Terreus for the Production of Natural Statins
    Journal of Fungi Review Exploitation of Aspergillus terreus for the Production of Natural Statins Mishal Subhan 1, Rani Faryal 1 and Ian Macreadie 2,* 1 Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan; [email protected] (M.S.); [email protected] (R.F.) 2 School of Science, RMIT University, Bundoora, Victoria 3083, Australia * Correspondence: [email protected]; Tel.: +61-3-9925-6627 Academic Editor: David S. Perlin Received: 19 April 2016; Accepted: 26 April 2016; Published: 30 April 2016 Abstract: The fungus Aspergillus (A.) terreus has dominated the biological production of the “blockbuster” drugs known as statins. The statins are a class of drugs that inhibit HMG-CoA reductase and lead to lower cholesterol production. The statins were initially discovered in fungi and for many years fungi were the sole source for the statins. At present, novel chemically synthesised statins are produced as inspired by the naturally occurring statin molecules. The isolation of the natural statins, compactin, mevastatin and lovastatin from A. terreus represents one of the great achievements of industrial microbiology. Here we review the discovery of statins, along with strategies that have been applied to scale up their production by A. terreus strains. The strategies encompass many of the techniques available in industrial microbiology and include the optimization of media and fermentation conditions, the improvement of strains through classical mutagenesis, induced genetic manipulation and the use of statistical design. Keywords: Aspergillus terreus; compactin; fermentation; industrial microbiology; lovastatin; mevastatin; mutagenesis; optimization; polyketide 1. Introduction Statins are polyketide compounds that are produced by some fungi during their secondary metabolism [1].
    [Show full text]
  • Part1 Gendiff.Qxp
    Sex Differences in Health Status, Health Care Use, and Quality of Care: A Population-Based Analysis for Manitoba’s Regional Health Authorities November 2005 Manitoba Centre for Health Policy Department of Community Health Sciences Faculty of Medicine, University of Manitoba Randy Fransoo, MSc Patricia Martens, PhD The Need to KnowTeam (funded through CIHR) Elaine Burland, MSc Heather Prior, MSc Charles Burchill, MSc Dan Chateau, PhD Randy Walld, BSc, BComm (Hons) This report is produced and published by the Manitoba Centre for Health Policy (MCHP). It is also available in PDF format on our website at http://www.umanitoba.ca/centres/mchp/reports.htm Information concerning this report or any other report produced by MCHP can be obtained by contacting: Manitoba Centre for Health Policy Dept. of Community Health Sciences Faculty of Medicine, University of Manitoba 4th Floor, Room 408 727 McDermot Avenue Winnipeg, Manitoba, Canada R3E 3P5 Email: [email protected] Order line: (204) 789 3805 Reception: (204) 789 3819 Fax: (204) 789 3910 How to cite this report: Fransoo R, Martens P, The Need To Know Team (funded through CIHR), Burland E, Prior H, Burchill C, Chateau D, Walld R. Sex Differences in Health Status, Health Care Use and Quality of Care: A Population-Based Analysis for Manitoba’s Regional Health Authorities. Winnipeg, Manitoba Centre for Health Policy, November 2005. Legal Deposit: Manitoba Legislative Library National Library of Canada ISBN 1-896489-20-6 ©Manitoba Health This report may be reproduced, in whole or in part, provided the source is cited. 1st Printing 10/27/2005 THE MANITOBA CENTRE FOR HEALTH POLICY The Manitoba Centre for Health Policy (MCHP) is located within the Department of Community Health Sciences, Faculty of Medicine, University of Manitoba.
    [Show full text]
  • PI Changes for Fibrates
    Changes to Product Information as approved by the CHMP on 21 October 2010, pending endorsement by the European Commission 1 BEZAFIBRATE ANNEX I -SUMMARY OF PRODUCT CHARACTERISTICS 4.1 Therapeutic indications (to replace current text) [Product name] is indicated as an adjunct to diet and other non-pharmacological treatment (e.g. exercise, weight reduction) for the following: - Treatment of severe hypertriglyceridaemia with or without low HDL cholesterol. - Mixed hyperlipidaemia when a statin is contraindicated or not tolerated. 5.1 Pharmacodynamic properties (Additional text) There is evidence that treatment with fibrates may reduce coronary heart disease events but they have not been shown to decrease all cause mortality in the primary or secondary prevention of cardiovascular disease ANNEX III -LABELLING AND PACKAGE LEAFLET What [Product name] is and what it is used for [Product name] belongs to a group of medicines, commonly known as fibrates. These medicines are used to lower the level of fats (lipids) in the blood. For example the fats known as triglycerides. [Product name] is used, alongside a low fat diet and other non-medical treatments such as exercise and weight loss, to lower levels of fats in the blood. 2 CIPROFIBRATE ANNEX I -SUMMARY OF PRODUCT CHARACTERISTICS 4.1 Therapeutic indications (to replace current text) [Product name] is indicated as an adjunct to diet and other non-pharmacological treatment (e.g. exercise, weight reduction) for the following: - Treatment of severe hypertriglyceridaemia with or without low HDL cholesterol. - Mixed hyperlipidaemia when a statin is contraindicated or not tolerated. 5.1 Pharmacodynamic properties (Additional text) There is evidence that treatment with fibrates may reduce coronary heart disease events but they have not been shown to decrease all cause mortality in the primary or secondary prevention of cardiovascular disease ANNEX III -LABELLING AND PACKAGE LEAFLET What [Product name] is and what it is used for [Product name] belongs to a group of medicines, commonly known as fibrates.
    [Show full text]
  • Altoprev (Lovastatin)
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Liver enzyme abnormalities: Persistent elevations in hepatic These highlights do not include all the information needed to use transaminases can occur. Check liver enzyme tests before initiating ALTOPREV® safely and effectively. See full prescribing information for therapy and as clinically indicated thereafter. (5.2) Altoprev®. ------------------------------ADVERSE REACTIONS------------------------------­ ALTOPREV® (lovastatin extended-release) Tablets for oral The most commonly reported adverse reactions (incidence ≥ 5%) in patients administration treated with Altoprev® in placebo-controlled trials were: infection, headache Initial U.S. Approval: 2002 and accidental injury. (6.1) ----------------------------- RECENT MAJOR CHANGES------------------------- To report SUSPECTED ADVERSE REACTIONS, contact Watson at Warnings and Precautions (5) 10/2012 (1-800-272-5525) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. ----------------------------INDICATIONS AND USAGE--------------------------- Altoprev® is an HMG-CoA reductase inhibitor (statin) indicated as an ------------------------------DRUG INTERACTIONS------------------------------­ adjunctive therapy to diet to: • Reduce the risk of MI, revascularization procedures, and angina in Drug Interactions Associated with Increased patients without CHD, but with multiple risk factors. (1.1) Risk of Myopathy/Rhabdomyolysis (2.3 5.1, 7, 12.3) • Slow the progression of coronary atherosclerosis in patients with CHD Interacting Agents Prescribing Recommendations
    [Show full text]